Heterogeneity of proteins in commercial preparations of human chorionic gonadotropin (hCG) demonstrated by Western blotting.

Immunoblotting has been utilized to detect the presence of human chorionic gonadotropin (hCG), its alpha and beta subunits, the Tamm-Horsfall protein (uromodulin), immunoglobulins G (IgG) and M (IgM), kappa (K) and lambda (L) chains, and serum albumin in commercially available preparations of hCG intended for human use. Concentrated pregnancy, postpartum, and normal urines were studied as a comparison. Those hCG batches prepared from pooled first-trimester pregnancy urine contained all of the hCG and non-hCG proteins listed above or their fragments, with the single exception of the IgM mu chain. The conflicting literature regarding the immunomodulatory properties of hCG requires reevaluation, since many previous reports of immunologic activity utilized these preparations, containing intact and degraded IgG, K, and L chains, and the Tamm-Horsfall protein, all of which may contribute to an altered immune response. Since hCG can be prepared in high yields, free of these contaminants, these data suggest that patients are being unnecessarily exposed to contaminating substances when receiving parenteral injections of hCG.

Structure-activity relationships for steroid interaction with the gamma-aminobutyric acidA receptor complex.

Certain steroids are potent barbiturate-like modulators of the gamma-aminobutyric acidA (GABA) receptor-chloride ionophore complex in rat brain membranes. At nanomolar to low micromolar concentrations, these steroids stimulate [3H]flunitrazepam and [3H] muscimol binding and displace the convulsant [35S]t-butylbicyclophosphorothionate from its binding site in an allosteric manner, in addition to enhancing Cl- conductance responses to GABA recorded in cultured rat hippocampal and spinal neurons. A stringent structure-activity relationship exists for these interactions of steroids with the GABAA receptor complex. Comparison of the structure-activity relationship data obtained in this study with those for steroid-induced general anesthesia strongly suggests that steroidal anesthesia may result from the interaction between steroids and the GABAA receptor. The essential features of the active structures are a 5 alpha or 5 beta-reduced pregnane skeleton with a hydroxyl at C3 in the alpha-position and a ketone group at C20. These features are all present in some naturally occurring steroids, including metabolites of deoxycorticosterone and progesterone, that show potent activity at the GABAA receptor complex. Two of the compounds investigated are known to be formed in vivo as reduced metabolites of endogenous steroid hormones: 5 alpha-pregnane-3 alpha -ol-20-one and 5 alpha-pregnane-3 alpha,21-diol-20-one, which are derived from progesterone and deoxycorticosterone, respectively. These two steroids produce a striking prolongation of GABA-mediated inhibitory postsynaptic currents recorded at synapses between rat hippocampal neurons in culture and could conceivably regulate GABA-mediated inhibition under some physiologic and pathologic conditions.

Head and neck manifestations of gastroesophageal reflux.

Gastroesophageal reflux (GER) is a common condition with many manifestations which are of interest to the otolaryngologist. Factors predisposing to GER include anatomic abnormalities of the esophagus and pharynx, neurogenic disease and diet induced decreased lower esophageal sphincter pressure. Three interesting cases are reported, including subglottic stenosis which has not previously been thought to be a complication of GER. A literature review of otolaryngologic symptoms, the problems of diagnosis, and a suggested treatment plan are presented.